11-7565720-C-T

Variant names:

• chr11-7565720-C-T
• rs758341225
• NM_003621.5:c.232C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003621.5(PPFIBP2):​c.232C>T​(p.Pro78Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPFIBP2 NM_003621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76

Genes affected

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3661927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIBP2	NM_003621.5	c.232C>T	p.Pro78Ser	missense_variant	Exon 3 of 24	ENST00000299492.9	NP_003612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIBP2	ENST00000299492.9	c.232C>T	p.Pro78Ser	missense_variant	Exon 3 of 24	1	NM_003621.5	ENSP00000299492.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251306 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	.;D;D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.6	.;.;L;.
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.6	D;D;D;D
REVEL	Benign	0.15
Sift	Benign	0.036	D;D;T;T
Sift4G	Pathogenic	0.0	D;D;T;T
Polyphen		0.93	.;.;P;.
Vest4		0.63
MutPred		0.45		Gain of glycosylation at P78 (P = 0.027);Gain of glycosylation at P78 (P = 0.027);Gain of glycosylation at P78 (P = 0.027);Gain of glycosylation at P78 (P = 0.027);
MVP		0.48
MPC		0.23
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs758341225; hg19: chr11-7586951;